The Safety and Efficacy of MRG003 With or Without Putrelimab in Recurrent or Metastatic Salivary Gland Cancer: a Single-center, Open-label Cohort Study

Exclusion Criteria23

• A history of other malignancies within the past five years is exclusionary, except for adequately treated and cured cervical carcinoma in situ, thyroid cancer (excluding medullary or anaplastic types), or basal cell carcinoma of the skin.
• Prior receipt of any of the following treatments:
• Administration of an antibody-drug conjugate (ADC) with a monomethyl auristatin E (MMAE) payload within 3 months prior to first dose;
• Exposure to any investigational agent in a clinical trial within 28 days prior to first dose;
• Receipt of systemic anti-tumor therapy (including chemotherapy, radiotherapy, targeted therapy, or other modalities) within 28 days prior to first dose;
• Undergone major surgery within 28 days prior to first dose without full recovery, or scheduled to undergo major surgery during the first 12 weeks following initiation of study treatment.
• Patients with HER2-positive status at baseline who have not received HER2-targeted or combination therapy (including HER2 monoclonal antibody-based combinations, HER2 ADCs, or HER2-targeted small-molecule agents; receipt of any one of these is acceptable for enrollment).
• Presence of symptomatic central nervous system (CNS) metastases or leptomeningeal disease; or history of CNS metastasis treatment within 3 months prior to first dose.
• Clinically symptomatic pleural, peritoneal, or pericardial effusion requiring puncture drainage; except for patients with stable disease after symptomatic treatment, as determined by the investigator to be eligible for enrollment.
• Any severe or uncontrolled systemic illness, as determined by the investigator, including but not limited to poorly controlled hypertension (systolic blood pressure \>160 mmHg or diastolic blood pressure \>100 mmHg), inadequately controlled diabetes mellitus, or evidence of active bleeding.
• Poorly controlled cardiac disease, including heart failure of New York Heart Association (NYHA) class ≥2, unstable angina, myocardial infarction within the past year, or clinically significant supraventricular or ventricular arrhythmia requiring treatment.
• Active or uncontrolled infection, including:
• Hepatitis B virus (HBV): HBsAg positive and HBV DNA ≥2,000 IU/mL (with exclusion of drug-induced or other non-viral causes of hepatitis);
• Hepatitis C virus (HCV): anti-HCV antibody positive and detectable HCV RNA above the assay's lower limit of quantification;
• Human immunodeficiency virus (HIV) infection;
• Uncontrolled bacterial, viral (non-HBV/HCV), fungal, rickettsial, or parasitic infections, unless resolved with appropriate treatment prior to first administration of study drug.
• History of hypersensitivity to Ptoridimab or any excipient in MRG003 (histidine, histidine hydrochloride, sucrose, mannitol, polysorbate 80), or prior grade ≥3 hypersensitivity reaction to monoclonal antibodies or other large protein therapeutics.
• Known history of primary immunodeficiency or active autoimmune disease requiring immunosuppressive therapy; current or recent (within 2 weeks before enrollment) use of systemic immunosuppressants or corticosteroids at a dose equivalent to ≥10 mg/day prednisone.
• Note: The following are permitted: type 1 diabetes mellitus with stable control; hypothyroidism managed with hormone replacement; vitiligo or psoriasis not requiring systemic therapy; use of topical or inhaled corticosteroids; or short-term (≤7 days) systemic corticosteroid use for non-autoimmune indications such as allergy prophylaxis or acute inflammation.
• History of or concurrent moderate-to-severe interstitial lung disease, radiation pneumonitis, severe chronic obstructive pulmonary disease, severe pulmonary insufficiency, or symptomatic bronchospasm.
• Failure to recover from prior anti-cancer therapy-related toxicities to Grade ≤1 according to NCI-CTCAE v5.0, excluding alopecia, any degree of skin hyperpigmentation, or stable Grade 2 hypothyroidism on hormone replacement.
• Peripheral neuropathy of Grade \>1.
• Any other condition that, in the investigator's judgment, contraindicates participation in the study, including substance abuse (e.g., alcoholism, drug addiction), or inability to comply with study procedures.